Subtitles and Transcript

Grégoire Courtine

0:11
I am a neuroscientistwith a mixed background in physics and medicine.My lab at the Swiss Federal Institute of Technologyfocuses on spinal cord injury,which affects more than 50,000 peoplearound the world every year,with dramatic consequences for affected individuals,whose life literally shattersin a matter of a handful of seconds.

0:39
And for me, the Man of Steel,Christopher Reeve,has best raised the awarenesson the distress of spinal cord injured people.And this is how I started my own personal journeyin this field of research,working with the Christopher and Dana Reeve Foundation.

0:57
I still remember this decisive moment.It was just at the end of a regular day of workwith the foundation.Chris addressed us, the scientists and experts,"You have to be more pragmatic.When leaving your laboratory tomorrow,I want you to stop by the rehabilitation centerto watch injured peoplefighting to take a step,struggling to maintain their trunk.And when you go home,think of what you are going to change in your researchon the following day to make their lives better."

1:33
These words, they stuck with me.This was more than 10 years ago,but ever since, my laboratory has followedthe pragmatic approach to recoveryafter spinal cord injury.And my first step in this directionwas to develop a new model of spinal cord injurythat would more closely mimic some of the key features of human injurywhile offering well-controlled experimental conditions.And for this purpose, we placed two hemisectionson opposite sides of the body.They completely interrupt the communicationbetween the brain and the spinal cord,thus leading to complete and permanent paralysisof the leg.But, as observed, after most injuries in humans,there is this intervening gap of intact neural tissuethrough which recovery can occur.But how to make it happen?

2:24
Well, the classical approachconsists of applying interventionthat would promote the growth of the severed fiberto the original target.And while this certainly remained the key for a cure,this seemed extraordinarily complicated to me.To reach clinical fruition rapidly,it was obvious:I had to think about the problem differently.

2:51
It turned out that more than 100 years of researchon spinal cord physiology,starting with the Nobel Prize Sherrington,had shown thatthe spinal cord, below most injuries,contained all the necessary and sufficient neural networksto coordinate locomotion,but because input from the brain is interrupted,they are in a nonfunctional state, like kind of dormant.My idea: We awaken this network.

3:18
And at the time, I was a post-doctoral fellow in Los Angeles,after completing my Ph.D. in France,where independent thinkingis not necessarily promoted.(Laughter)I was afraid to talk to my new boss,but decided to muster up my courage.I knocked at the door of my wonderful advisor,Reggie Edgerton, to share my new idea.

3:45
He listened to me carefully,and responded with a grin."Why don't you try?"

3:52
And I promise to you,this was such an important moment in my career,when I realized that the great leaderbelieved in young people and new ideas.

4:03
And this was the idea:I'm going to use a simplistic metaphorto explain to you this complicated concept.Imagine that the locomotor system is a car.The engine is the spinal cord.The transmission is interrupted. The engine is turned off.How could we re-engage the engine?First, we have to provide the fuel;second, press the accelerator pedal;third, steer the car.It turned out that there are known neural pathwayscoming from the brain that play this very functionduring locomotion.My idea: Replace this missing inputto provide the spinal cordwith the kind of interventionthat the brain would deliver naturally in order to walk.

4:46
For this, I leveraged 20 years of past research in neuroscience,first to replace the missing fuelwith pharmacological agentsthat prepare the neurons in the spinal cord to fire,and second, to mimic the accelerator pedalwith electrical stimulation.So here imagine an electrodeimplanted on the back of the spinal cordto deliver painless stimulation.It took many years, but eventually we developedan electrochemical neuroprosthesisthat transformed the neural networkin the spinal cord from dormant to a highly functional state.Immediately, the paralyzed rat can stand.As soon as the treadmill belt starts moving,the animal shows coordinated movement of the leg,but without the brain.Here what I call "the spinal brain"cognitively processes sensory informationarising from the moving legand makes decisions as to how to activate the musclein order to stand, to walk, to run,and even here, while sprinting,instantly standif the treadmill stops moving.

5:59
This was amazing.I was completely fascinated by this locomotionwithout the brain,but at the same time so frustrated.This locomotion was completely involuntary.The animal had virtually no control over the legs.Clearly, the steering system was missing.And it then became obvious from methat we had to move awayfrom the classical rehabilitation paradigm,stepping on a treadmill,and develop conditions that would encouragethe brain to begin voluntary control over the leg.

6:36
With this in mind, we developed a completely newrobotic system to support the ratin any direction of space.Imagine, this is really cool.So imagine the little 200-gram ratattached at the extremity of this 200-kilo robot,but the rat does not feel the robot.The robot is transparent,just like you would hold a young childduring the first insecure steps.

7:05
Let me summarize: The rat receiveda paralyzing lesion of the spinal cord.The electrochemical neuroprosthesis enableda highly functional state of the spinal locomotor networks.The robot provided the safe environmentto allow the rat to attempt anythingto engage the paralyzed legs.And for motivation, we used what I thinkis the most powerful pharmacology of Switzerland:fine Swiss chocolate.

7:35
(Laughter)

7:38
Actually, the first results were very, very,very disappointing.Here is my best physical therapistcompletely failing to encourage the ratto take a single step,whereas the same rat, five minutes earlier,walked beautifully on the treadmill.We were so frustrated.

8:07
But you know, one of the most essential qualitiesof a scientist is perseverance.We insisted. We refined our paradigm,and after several months of training,the otherwise paralyzed rat could stand,and whenever she decided,initiated full weight-bearing locomotionto sprint towards the rewards.This is the first recovery ever observedof voluntary leg movementafter an experimental lesion of the spinal cordleading to complete and permanent paralysis.

8:41
In fact --

8:43
(Applause)

8:44
Thank you.

8:49
In fact, not only could the rat initiateand sustain locomotion on the ground,they could even adjust leg movement,for example, to resist gravityin order to climb a staircase.I can promise you this wassuch an emotional moment in my laboratory.It took us 10 years of hard workto reach this goal.

9:12
But the remaining question was, how?I mean, how is it possible?And here, what we foundwas completely unexpected.This novel training paradigmencouraged the brain to create new connections,some relay circuitsthat relay information from the brainpast the injury and restore cortical controlover the locomotor networks below the injury.And here, you can see one such example,where we label the fibers coming from the brain in red.This blue neuron is connected with the locomotor center,and what this constellationof synaptic contacts meansis that the brain is reconnected with the locomotor centerwith only one relay neuron.But the remodeling was not restrictedto the lesion area.It occurred throughout the central nervous system,including in the brain stem,where we observed up to 300-percent increasein the density of fibers coming from the brain.We did not aim to repair the spinal cord,yet we were able to promoteone of the more extensive remodelingof axonal projections ever observedin the central nervous system of adult mammalafter an injury.

10:35
And there is a very important messagehidden behind this discovery.They are the result of a young teamof very talented people:physical therapists, neurobiologists, neurosurgeons,engineers of all kinds,who have achieved togetherwhat would have been impossible by single individuals.This is truly a trans-disciplinary team.They are working so close to each otherthat there is horizontal transfer of DNA.We are creating the next generationof M.D.'s and engineerscapable of translating discoveries all the wayfrom bench to bedside.And me?I am only the maestro who orchestrated this beautiful symphony.

11:27
Now, I am sure you are all wondering, aren't you,will this help injured people?Me too, every day.The truth is that we don't know enough yet.This is certainly not a cure for spinal cord injury,but I begin to believe that this may leadto an intervention to improve recoveryand people's quality of life.

11:57
I would like you allto take a moment and dream with me.Imagine a person just suffered a spinal cord injury.After a few weeks of recovery,we will implant a programmable pumpto deliver a personalized pharmacological cocktaildirectly to the spinal cord.At the same time, we will implant an electrode array,a sort of second skincovering the area of the spinal cord controlling leg movement,and this array is attached to an electrical pulse generatorthat delivers stimulations that are tailoredto the person's needs.This defines a personalized electrochemical neuroprosthesisthat will enable locomotionduring training with a newly designed supporting system.And my hope is that after several months of training,there may be enough remodeling of residual connectionto allow locomotion without the robot,maybe even without pharmacology or stimulation.My hope here is to be able to createthe personalized conditionto boost the plasticity of the brainand the spinal cord.And this is a radically new conceptthat may apply to other neurological disorders,what I termed "personalized neuroprosthetics,"where by sensing and stimulating neural interfaces,I implanted throughout the nervous system,in the brain, in the spinal cord,even in peripheral nerves,based on patient-specific impairments.But not to replace the lost function, no --to help the brain help itself.

13:45
And I hope this enticed your imagination,because I can promise to youthis is not a matter of whether this revolution will occur,but when.And remember, we are only as greatas our imagination, as big as our dream.